TABLE 1

Murine studies investigating cytokine and protease levels after e-cigarette exposure. Summary of murine studies investigating inflammatory cytokine and protease levels in BAL fluid following e-cigarette exposures of varying lengths, in comparison to air exposed control mice. Representative examples of acute, subacute and chronic murine cigarette smoke exposure models are included for comparison.

Author [ref.]	Year	E-cigarette specification	ECL details	Exposure regime	Cells in BAL	Cytokines in BAL
						Increased	Unchanged	Decreased
Sussan [44]	2015	NJOY vape pen	18 mg·mL⁻¹	1.5 h twice per day, 14 days	No increase in neutrophil, eosinophil or lymphocyte count Increased macrophage count		MCP-1	IL-6
Lerner [42]	2015	Blu vape pen	16 mg·mL⁻¹	5 h·day⁻¹, 3 days	No increase in macrophage count	IL-6, IL-1α, IL-13, MCP-1	IL-10,^# IL-1β,^# KC,^# IL-17, GMCSF, CXCL10, MIP2
Wang [45]	2020	Joytech box-mod	25 mg·mL⁻¹ (0 mg·mL⁻¹ control arm)	2 h·day⁻¹, 30 days	Increase in macrophage, CD4 T-cell and CD8 T-cell count No increase in neutrophil count	MCP-1,^¶ IL-1α,^¶ TNFα,^¶ GMCSF,^¶ MIP-1B,^¶ IL-2,^¶ IL-5,^¶ IL-9,^¶ IFNγ,^¶ RANTES^¶
Hwang [43]	2016	Vape pen	24 mg·mL⁻¹	1 h·day⁻¹, 28 days	No increase in macrophage, neutrophil, eosinophil or lymphocyte counts	KC, IL1rα		GMCSF, IL-3
Madison [46]	2019	Vape pen/box-mod	33 mg·mL⁻¹	6 min·day⁻¹, 4 months	No increase in macrophage, neutrophil or lymphocyte count No increase in dendritic cell or Th17 cell count	Not investigated	Not investigated	Not investigated
Vlahos [47]	2006	Commercially available filter-tipped cigarettes		3, 6 or 9 cigarettes per day, 4 days	Dose-dependent neutrophil increase Increased macrophages with 9 cigarettes per day No increase in lymphocyte count	TNFα,⁺ MIP2,⁺ IL-6,⁺ GMCSF⁺	IL-10⁺
Beckett [50]	2013	3R4F reference cigarettes		Twice per day, 5 times per week, 1–12 weeks	Increased macrophage and neutrophil count at 4 days and 8 weeks Increased lymphocyte count at 8 weeks	TNFα,⁺ IL-1β,⁺ CXCL1⁺
Phillips [51]	2015	3R4F reference cigarettes		1 h 4 times per day, 5 days per week, 7 months	Increased macrophage, neutrophil, lymphocyte and dendritic cell count	GMCSF, IFNγ, IL-1α, IL-6, IP10, MCP1 TNFα, MIP1, MIP2	IL-10, IL-1β
Motz [52]	2010	3R4F reference cigarettes		4 h·day⁻¹, 5 days per week, 24 weeks	Increased macrophage/monocyte, neutrophil and lymphocyte count	Not presented	Not presented

ECL: e-cigarette liquid; BAL: bronchoalveolar lavage; MCP: monocyte chemoattractant protein; IL: interleukin; KC: keratinocyte-derived chemokine; GMCSF: granulocyte-macrophage colony-stimulating factor; CXCL: chemokine (C-X-C motif) ligand; MIP: macrophage inflammatory protein; TNF: tumour necrosis factor; IFN: interferon; RANTES: regulated on activation, normal T-cell expressed and secreted. ^#: Trends suggest increased levels bordering on significance; ^¶: changes dependent on nicotine in ECL; ⁺: gene expression levels in whole lung tissue.